Thiosemicarbazones

ABSTRACT

The present invention relates to novel compounds of the formula:   WHEREIN R is a member selected from the group consisting of   D R A W I N G

United States Patent [191 Addor et al.

[ 1 Sept. 25, 1973 THIOSEMICARBAZONES [75] Inventors: Roger Williams Addor, Pennington; Glentworth Lamb, Trenton, both of NJ.

American Cyanamid Company, Stamford, Conn.

[22] Filed: Feb. 17, 1972 [21] Appl. No.: 227,287

[73] Assignee:

[52] US. Cl. 260/327 M, 424/277 [51] Int. Cl. A6lk 27/00, C07d 71/00 [58] Field of Search 260/327 M, 340.7,

[56] References Cited UNITED STATES PATENTS 7/1965 Addor ..260/327 9/l969 Addor ..260/327 Primary ExaminerHenry R. Jiles Assistant ExaminerCecilia M. S. Jaisle Attorney-Robert P. Raymond 5 7 ABSTRACT The present invention relates to novel compounds of the formula:

wherein R is a member selected from the group consisting of 12 Claims, No Drawings THIOSEMICARBAZONES This invention relates to novel compounds having the formula:

wherein R is a member selected from the group consisting of JR-( JR (111' (mu I I 1 3. 3 93 3 and the Rs are independently hydrogen or lower alkyl of C It further relates to a method for controlling fungi with the above-identified compounds and to the use of such compounds for protecting agronomic crops, both growing and harvested, from attack by pathogenic fungus organisms.

The above compounds can be synthesized by reacting the acid salt of the appropriate 2-imino derivative of 1,3-dithiole, l,3-dithiolane or l,3-dithiane and thiosemicarbazide or the appropriate derivative thereof.

Reaction is conveniently induced by admixing the iminodithiole, dithiolane or dithiane with the selected thiosemi-carbazide in sufficient amount to provide a mole ratio of the heterosulfur compound to the thiosemicarbazide of from 1:1.5 to 1.5 to l. The temperature of the mixture is maintained between about 50C. and 125C. The pH of the reaction mixture is maintained below 7.0. The reaction is conducted in the presence of a solvent selected from the group consisting of water, lower alkyl alcohols and mixtures thereof. Suitable loweralkyl alcohols include methanol, ethanol, isopropanol, n-propanol, n-butanol and 2-butanol.

In a preferred embodiment of the above process approximately equimolar amounts of the hetero sulfur compound and the thiosemicarbazide are utilized. Also, the temperature of the reaction mixture is preferably maintained between about 75C. and 70C., the pH is maintained between 1.0 to 6.0 and the preferred solvent is water.

Moreover, it has been found that the bisulfate, hydrochloride and hydrobromide salts of the 2-iminodithioles dithiolanes or dithianes may be used in the instant process, however, the bisulfate salts appear to be the preferred species.

These reactions may be graphically written as follows:

wherein R and R are as defined above and X is SO, Br or Cl.

Illustrative compounds of Formula I include, for example, 4-methyl-l,3-dithiolan--2-one thiosemicarbazone, 4,5-dimethyl-1,3-dithiolan-2-one thiosemicarbazone, 4-n-butyl-l,3-dithiolan-2-one thiosemicarbazone, l,3-dithian-2-one thiosemicar-bazone, 4,4- dimethyl-l ,3-dithiolan-2-one thiosemicarbazone, 1,3- dithiolan-2-one thiosemicarbazone, 4-methyl-l,3-

dithiol-2-one thiosemicarbazone, 'l,3-ditleiolan-2-one 4-methylthiosemicarbazone, 4-ethyl-l,3-dithiolan- 2-one thiosemicarbazone, 1,3-dithiolan-2-one 4,4- dibutyl thiosemicarbazone, 4,4,5,5-tetramethyl-1.3-dithiolan-2-one thiosemicarbazone, 4,5-dimethyl-l,3- dithiol-2-one thiosemicarbazone, 4-methyll ,3-dithian- 2-one thiosemicarbzone, 4,5,6-trimethyl-l,3-clithian- 2-one thiosemicarbazone, and the like.

Methods for the preparation of the 2-imino-l,3- dithioles, 2-imino-l,3-dithiolanes and 2-imino-1 ,3- dithianes (i.e., the starting materials for the compounds of the present invention) are described in the Addor U.S. Pat. Nos. 3,l97,48l, 3,364,230, 3,389,147, 3,193,561, and the Lies U.S. Pat. Nos. 3,342,835 and 3,449,366.

For use in controlling fungi, the above compounds are brought into contact with the fungi to be controlled. For ease in application, one or more of the active ingredients is preferably formulated in effective or fungitoxic amount with a conventional agricultural adjuvant, such as a solid or liquid inert carrier, diluent or other formulation aid.

For use in the treatment or protection of growing plants or agronomic crops from pathogenic fungi, the compounds are applied to the crops to be protected. The compounds are preferably formulated as dusts, dust concentrates, wettable powders or the like, and applied by conventional equipment, as by spraying or dusting the foliage of said plants or harvested crops.

Dusts are usually prepared by grinding together from about 1 to 15 percent by weight of the active ingredient and from about 99 to percent by weight of a finely divided inert diluent or carrier. Kaolin, attapulgite, diatomaceous earth, talc and fullers earth are typical carriers useful in the preparation of such dust formulations. if desired, it has also been found that sticking agents may be incorporated in these formulations but are not essential.

Dust concentrates are prepared in the same manner as the more dilute dusts but generally contain from about 25 to percent by weight of the toxicant. In addition to the grinding method referred to above, it is noted that these formulations may also be prepared by dissolving the toxicant in hot acetone or methylene chloride and spraying the toxicant solution on a tumbling bed of a finely divided solid inert carrier. Any of the solid carriers described above may be employed in these formulations.

wettable powders are usually prepared in the same manner as the dust formulations excepting that in addition to the toxicant and carrier there is also generally added from about 1 to 5 percent by weight of a dispersing agent such as an alkali metal lignosulfonate and from about 1 to 5 percent by weight of a wetting agent. Wetting agents such as sodium N-methyl-N- oleoyltaurate and sodium alkylnaphthalene sulfonate are suitable for this purpose.

In practice, the wettable powders are generally dispersed in water or other relatively inexpensive liquid such as deodorized derosene and applied to the crops sought to be protected, as liquid sprays. From about 20 to 400 gallons of liquid, containing from about onefourth to 8 lbs. of active ingredient is generally used per acre of crops being treated.

Typical wettable powder formulations are set forth in Table 1 below:

ethanol Attaclay by the Attapulgus Clay Company The invention and preparation of the active ingredients are further illustrated by the examples set forth below. Which are not to be taken as being limitative thereof. Unless otherwise specified, all parts and percentages are by weight.

EXAMPLE 1 Preparation of 4-methyl-l,3-dithio1an-2-one thiosemicarbazone S CH3 NH-HC1 NH2NHCSNH2 4-Metyl-2-imino-l ,3-dithio1ane hydrochloride (12.0 g., 0.0707 mole) was dissolved in 100 ml. of water and filtered into a 500 ml. round-bottomed flask equipped with a mechanical stirrer, reflux condenser, and thermometer. Thiosemicarbazide (6.45 g., 0.0707 mole) was added with stirring and the reaction mixture was heated on a steam bath to 70C. and held there for about 5 minutes. During the heating, complete solution was observed before the product precipitated. After slow cooling and standing for 2 hours, the white solid was collected on a Buchner funnel, washed with water,

and dried in a vacuum desiccator over KOH to give 7.3 g., m.p. 163-l64C.

A second crop, which crystallized in the mother liquor, was filtered, washed, and dried: wt., 1.2 g., m.p. l62-163C. The combined crops (8.5 g., 58 percent yield) were recrystallized from 250 ml. of absolute ethanol to give 7.2 g., m.p. 163l64C. (with bubbling).

Anal. Calcd. for C H N S C, 28.96; H, 4.38; N, 20.27; S, 46.40 Found; C 28.75; H, 4.40; N, 20.09; S, 46.37.

After standing for a week, the reaction mother liquor yielded an additional 4.6 g. of long needles, m.p. l63-164C. (with bubbling), to bring the total yield to 90 percent.

For most of the compounds, the reaction mixture was allowed to stand overnight before filtration of crude product, and no attempt was made to recover further crops.

EXAMPLE 2 Preparation of 4-methyl-l,3-dithiol-2-one thiosemicarbazone To the imino compound hydrochloride (0.15 mole, 30.8 g.) in 200 ml. of water was added thiosemicarbazide (0.15 mole, 13.7 g.). The reaction mixture was heated to 85C when solid began to precipitate. The mixture was cooled and allowed to stand. Several solid crops formed. The best appeared to be third: wt., 3.7

g.,; m.p. 1l9.5124C.

Recrystallization from methanol gave 2.7 g. of yellow solid, m.p. 145.5-146C. Recrystallization from isopropanol gave 1.3 g. of off-white solid, m.p. l49-l5 1C.

Anal. Calcd. for C H N S C, 29.26; H, 3.44; N, 20.46; S, 46.85. Found: C, 29.40; H, 3.28; N, 20.54; S, 46.96.

EXAMPLES 3-8 By utilizing the procedure of Example 1 above and substituting the hydrochloride salt of the appropriate hetero sulfur compound and selected thiosemicarbazide for their appropriate counterparts, the compounds set forth in Table 11 below were prepared.

'r ABLE n Analysis Reaction Reaction Cnlcd Found lax. n0, tomporn- .\l.1., No. Compound minutes tur0,(.. (1 11 N S C II N S 3 CH;- S 10 05 180-183 3.2.55 501 18.0% 43.40 32.35 5.53 10.10 13.25

I: N NHCSNH; (1113* S 4 ll-C4119" S 10 74 137-130 38.5) 0.00 16.85 38.57 38.80 6.00 16.80 38.6

K =NNncs-Nm NNlICS*Nllz li (111.1 10 1121 1511 32.55 5.01 1x05 1310 33,021 5.3" 13.8. 131i TABLE 11 .-Continued Analysis Reaction Reaction Coicd. Found Ex. time, temperw M.P., N 0. Compound n1 lnutes ture, C. C. C II N S C H N S I: 3 Nikos NIP-(311a K -'-:N--NH -CS NlIz 4 Mel ts with decomposition.

EXAMPLES 9-13 diately thereafter the inoculated plants were placed in 15 a constant temperature cabinet at 62F. and a saturated Following the procedure of Example 1 or 2 above, atmosphere. After 24 hours the temperature was adthe following reactions are effected. The compounds vanced to 70F. and held there for 72 hours at which produced thereby are set forth in Table III below. time the plants were removed to the green-house.

R S /R? A H: =NH-HX NH,NHCS-N -1 S \Rs Solvent l 5 T Rfl' s H =N-NI1-CN\ Rm? s 111 TABLE III Substituents Mole Reaction ratio, Ra Ra R10 temp. Solvent A:B

11 11 Calls 90 1110 1:1 011: C3115 C1115 H1O 1:1 10311; 10,111 H 65 0111011 1=1.s 11 II c111, 118 BuOH 1=1 @113 CH: CH: 80 20 011 011 1.521

EXAMPLES 14-21 Readings on disease control were made 7 days after inoculation, using the following ratings of disease ob- Following the procedure of Example 1 above the folserved: 5 no disease; 4 trace; 3 slight; 2 lowing reactions are effected. The compounds promoderate; 1 severe disease. The results are set forth duced thereby are set forth in Table [V below. 40 in Table V below.

TABLE 1\' 112 /R1 1t,\ /1t1 1(7 1(7 1n c). s Solvent 1o c .s :NlLllX NIIZNHGSN\ =NNHCS\ /Y c 1) R3 F 1t;

R5 R5 R5 110 Substituents Mole Temp, ratio. R4 R1 R6 R7 Rs 1! Solvent Cal) 11 11 11 11 11 1 1120 111 cm 11 11 11 C211. 0 .10 1110 0113011 1:1 11 11 C113 C113 11 0 J0 H2 '1 6113011 111.5 11 11 11 11 11 0 so 1120 1:115 11 c2115 c211 11 11 1 73 0211.011 111 11 i-Cgll: 11 11 11 1 111 03111011 11 11 11 can 11 c4119 0 11s 0.111011 1.5;1 (1111 C11; C11: c113 0111 1 65 0113011 1=1 EXAMPLE 22 60 TABLE V Results of Foliar Spray Protective Tests The follage of Bonme Best Tomato plants with 4 true leaves, and Early Marketeer cucumber plants with 2 1 Disease true leaves were sprayed with 50/50 acetone/water so- Tom la te bligl1t lutions containing ppm. or 500 ppm. of test com- 0 d 00 00 00 100 pound. All plants were sprayed to run-off. The plants 5 ompom' were allowed to dry and were then sprayed with a 4 3 5 4 mixed inoculum of Phytophthora infestans (late blight) s Ulla-f =NNIICS-N1h and Colletotrichum lagenarium (anthracnose). lmmes TABLE -(ontinucd Results of Follnr Spray Protective Tests Disease rating Cuc. anthrac. Tom late blight Four groups of tobacco plants (Hurley variety 20 plants per group), approximately two weeks old and previously inoculated with the disease organism Peronospora tabacina, are sprayed with a 35/65 percent acetone/water mixture containing 50 or 200 ppm. of test compound. The sprayed plants are placed in an incubator maintained at 2025C. for 6 days and then removed and examined for disease symptoms. Zineb, a commercial fungicide, and inoculated untreated plants, are used as controls. Data observed are reported as percent control in Table VI below.

TABLE VI Rate, Percent Compound p.p.m. control q S 50 30. 200 D6. 3

-N --Nn c- Nlh Zlncb 50 31.3 200 78. 8

Inoculated check 0.0

We claim: 1. A compound having the formula selected from the group consisting of:

wherein R is a member selected from the group consisting of I l l I l o R= CR, omen: and o RZC Room,

and the Rs are independently hydrogen or lower 0f C1-C4. 2. A compound according to claim 1 having the for- 3. A compound according to claim 1 having the formula:

4. A compound according to claim 1 having the formula:

5. A compound according to claim 1: 4methyl-1,3- dithiolan-Z-one thiosemicarbazone.

6. A compound according to claim 1: 4,5-dimethyll,3-dithiolan-2one thiosemicarbazone.

7. A compound according to claim 1: 4-n-butyl-1 ,3- dithiolan-Z-one thiosemicarbazone.

8. A compound according to claim 1: l,3-dithian- 2-one thiosemicarbazone.

9. A compound according to claim 1: 4,4-dimethyll,3-dithiolan-2-one thiosemicarbazone.

10. A compound according to claim 1: 1,3-dithiolan- 2-one thiosemicarbazone.

11. A compound according to claim 1: 4-methyl-l ,3- dithiol-Z-one thiosemicarbazone.

12. A compound according to claim 1: 1,3-dithiolan- 2-one 4-methylthiosemicarbazone. 

2. A compound according to claim 1 having the formula:
 3. A compound according to claim 1 having the formula:
 4. A compound according to claim 1 having the formula:
 5. A compound according to claim 1: 4-methyl-1,3-dithiolan-2-one thiosemicarbazone.
 6. A compound according to claim 1: 4,5-dimethyl-1,3-dithiolan-2-one thiosemicarbazone.
 7. A compound according to claim 1: 4-n-butyl-1,3-dithiolan-2-one thiosemicarbazone.
 8. A compound according to claim 1: 1,3-dithian-2-one thiosemicarbazone.
 9. A compound according to claim 1: 4,4-dimethyl-1,3-dithiolan-2-one thiosemicarbazone.
 10. A compound according to claim 1: 1,3-dithiolan-2-one thiosemicarbazone.
 11. A compound according to claim 1: 4-methyl-1,3-dithiol-2-one thiosemicarbazone.
 12. A compound according to claim 1: 1,3-dithiolan-2-one 4-methylthiosemicarbazone. 